immunosuppressants Flashcards
rheumatoid arthritis pathophysiology
Inflammatory change and proliferation of synovium
leading to dissolution of cartilage and bone
can lead to erosion of the joint
more expression of pro inflammatory cytokines (IL1,IL6, TNFalpha)
antibodies produced by B cells: Rheumatoid factor, Anti-CCP antibodies
clinical criteria for Ra
• Morning stiffness more than 1 hour • Arthritis of more than 3 joints • Arthritis of hand joints • Symmetrical arthritis • Rheumatoid nodules
non-clinical criteria for RA
• Serum rheumatoid factor/Anti-CCP antibodies • X-ray changes
treatment goals
Symptomatic relief Prevention of joint destruction
treatment strategies for Ra
• Early use of disease-modifying drugs • Aim to achieve good disease control • Use of adequate dosages • Use of combinations of drugs • Avoidance of long-term corticosteroids drug induced remission
Treatment goals in SLE & vasculitis
- Symptomatic relief e.g arthralgia, Raynaud’s phenomenon
- Reduction in mortality
- Prevention of organ damage
- Reduction in long term morbidity caused by disease and by drugs
corticosteroids mechanism
Upregulate anti-inflammatory and downregulate pro-inflammatory genes
(• Prevent interleukin IL-1 and IL-6 production by macrophages • Inhibit all stages of T-cell activation)
corticosteroid examples
Non-biologics • Sulphasalazine gut and joint • Hydroxychloroquine lupus, immuno modulatory effect Biologics • Anti-TNF agents • Rituximab • IL-6 inhibitors, JAK inhibitors
Azathioprine indication
• SLE & vasculitis -as maintenance therapy
steroid sparing drug
atopic dermatitis, bulbous skin disease
Azathioprine mechanism
• metabolized by TPMT
• TPMT gene highly polymorphic Low/absent TPMT levels = Risk of
myelosupression • Therefore test TPMT activity before prescribing
Inhibits synthesis of purines needed for DNA and RNA replication
#Azathioprine (All immunosuppressants)
• Bone marrow suppression – Monitor FBC • Increased risk of malignancy • Increased risk of infection • Hepatitis – Monitor LFT
Other immunosuppressants -caution
Calcineurin inhibitor examples
Ciclosporin & tacrolimus
Calcineurin inhibitor indication
transplantation, atopic dermatitis, psoriasis
Calcineurin inhibitor
renal toxicity, gum hypertrophy
check BP, eGRF regularly
^ Calcineurin inhibitor
CYP 450 drugs inducers and inhibitors